Thursday, January 1, 2026 1/1/2026

ATIC is a novel molecular target in diffuse intrinsic pontine glioma

Award Number: R01NS132884
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/09/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2028

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ATIC is a novel molecular target in diffuse intrinsic pontine glioma - Abstract Diffuse intrinsic pontine glioma (DIPG) is an incurable childhood cancer. Median survival after diagnosis is less than 2 years, and 5‐year overall survival is only 1%. DIPGs are inoperable, and xenograft models of autopsy tissue-derived cell lines are the mainstay for molecular studies. To identify novel molecular targets, we performed the first untargeted metabolomics of DIPG. We used Network Integration with published DIPG gene expression data, and our own gene expression data of DIPG lines to visualize and interpret changes in DIPG metabolome. Our preliminary studies uncovered a novel molecular target in DIPG. Our strong in vitro and in vivo data indicates that the DIPG mutation H3K27M upregulates the de novo purine metabolism enzyme ATIC which is a new therapeutic target in DIPG. We observed that while ATIC knockout by CRISPR greatly improved survival in mice with DIPG tumors, an antifolate ATIC inhibitor alone was not very effective in reducing DIPG growth. Through further metabolomics analysis we identified the potential mechanism of antifolate drug resistance in DIPG and combination strategies to overcome antifolate resistance. In this application, using molecular and genetic tools, antifolates and inhibitors of one carbon metabolism we will examine the extent and biological consequences of ATIC inhibition on de novo purine biosynthesis, DIPG growth and dissemination and overall animal survival in two independent mouse models of DIPG.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $373,226 )
2026	2026	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	12/12/2025	NON-COMPETING CONTINUATION	$373,226
														Subtotal = $373,226

Issue Date FY: 2025 ( Subtotal = $420,186 )
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	2	3/28/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	2	2/12/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$287,640
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	11/18/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$420,186
2025	2023	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	11/15/2024	NEW	$0
2025	2023	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	1	2/12/2025	NEW	-$287,640
														Subtotal = $420,186

Issue Date FY: 2023 ( Subtotal = $484,167 )
2023	2023	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/7/2023	NEW	$484,167
														Subtotal = $484,167

Grand Total All Awards = $1,277,579

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ATIC is a novel molecular target in diffuse intrinsic pontine glioma

Award Number: R01NS132884

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/09/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2028

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